This reseaach proposal is concerned with the role of lymphokines in hypersensitivity granulomatous lung reactions. The main objective is to investigate the role of partially purified chemotactic and migration inhibitory factors in macrophage mediated tissue injury and repair (macrophage-fibroblast interaction). The research objectives are divided into the following areas: 1. Production of lymphokine-rich supernatants from a) antigen-stimulated artifical hypersensitivity granulomas isolated from the lungs of sensitized, challenged animals, and b) antigen-stimulated spleens of Schistosoma mansoni infected mice. 2. Fractionation by gel filtration and purification by isoelectric focusing of the crude, active supernatants. Examination of the fractions for chemotactic and migration inhibitory activity, determination of molecular size, heat neuraminidase and chymotrypsin sensitivity and the elicitation of elevated 1-14C glucose oxidation in macrophages. 3. Injection of fluid lymphokines or lymphokines bound covalently to Sepharose beads into the lungs of normal mice and quantitation of the elevated levels of several lysosomal enzymes and lysozyme in the alveolar and granuloma macrophages. Examination of the effect of crude lysosomal enzymes covalently bound onto beads, and i.v. injected on lung pathology. 4. Determination of the collagenase and elastase content of activated alveolar and granuloma macrophage and examination of the effect of these cells and their products on the 14C-labelled collagen synthesizing ability of normal and activated syngeneic fibroblasts in vitro. 5. Suppression of the granulomatous inflammation with the aid of anti-lymphokine serum.